Dutasteride for the Reduction of Alcohol Use in Male Drinkers

• Sponsor: UConn Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01262287
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 47
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether dutasteride is safe and effective for reducing alcohol use in male drinkers who want to stop or reduce their drinking. The investigators hypothesize that at a dosage of 1mg/day, dutasteride will be well tolerated and that, compared to placebo treatment, dutasteride will result in a greater reduction in the amount of alcohol consumed per week. The study sample size is of a pilot scale and is designed to provide additional support for the study hypothesis and provide an estimate of likely effect sizes in order to design a more definitive study.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism; Alcohol Abuse; Alcohol Dependence	Drug: Dutasteride; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Placebo Controlled Pilot Study of Dutasteride for the Reduction of Alcohol Use in Male Drinkers
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dutasteride dutasteride (1 mg oral daily dose) for 8-week treatment period	Drug: Dutasteride; dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period; Other Names: Avodart
Placebo Comparator: Placebo placebo daily for 8-week treatment period	Drug: Placebo; placebo capsules in same number as active drug, daily for 8-week treatment period; Other Names: Lactose

Outcome Measures

Primary Outcome Measures

1. Change Number of Standard Drinks Per Week. [Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment)]

   Change in Average Standard Drinks (14 gr ethanol) per week: last 2 weeks of treatment (wk 7-8) minus baseline average drinking average from baseline 90 day drinking history

Secondary Outcome Measures

1. Change in Standard Drinks Per Week - Moderation by Genetic Variation [Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment)]

   Moderation of primary outcome measure [change in standard drinks per week from baseline to end point (average weeks 7 and 8 of treatment)] by genetic variation rs12529 in neuroactive steroid biosynthetic enzyme gene AKR1C (AKR1C3*2 C-allele associated with alcohol use disorder)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male outpatients age 18 to 65 years

• Have an average weekly ethanol consumption of >24 standard drinks

• Be able to read English at the 8th grade or higher level and show no evidence of significant cognitive impairment

• Be willing to nominate an individual who will know the patient's whereabouts in order to facilitate follow up during the study

• Be willing to provide signed, informed consent to participate in the study (including a willingness to reduce drinking to non-hazardous levels)

Exclusion Criteria:

• Have a current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation

• Have a serious psychiatric illness (e.g., schizophrenia, bipolar disorder, severe or psychotic major depression, organic mood or mental disorders, current eating disorder symptoms, or substantial suicide or violence risk) on the basis of history or psychiatric examination

• Have a current diagnosis of drug dependence (other than nicotine or alcohol dependence)

• Have a current diagnosis of alcohol dependence who on clinical examination by a physician, are deemed to be too severely alcohol dependent to permit them to participate in a placebo-controlled pilot study

• Have a history of hypersensitivity to dutasteride

• Current or past 4 month use of finasteride (Propecia), dutasteride (Avodart) or testosterone

• Are currently taking psychotropics other than a single antidepressant with stable dose for at least 4 weeks or a non-benzodiazepine sleep medication

• Are considered by the investigators to be an unsuitable candidate for receipt of an investigational drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Connecticut Health Center	Farmington	Connecticut	United States	06030

Sponsors and Collaborators

• UConn Health
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Jonathan Covault, MD, PhD, UConn Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonathan Covault, Professor of Psychiatry, UConn Health
• ClinicalTrials.gov Identifier: NCT01262287
• Other Study ID Numbers: 11-036-2; P60AA003510
• First Posted: Dec 17, 2010
• Last Update Posted: Mar 20, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jonathan Covault, Professor of Psychiatry, UConn Health: Randomized Trial; Medication for Heavy Drinking; Dutasteride Treatment
• Additional relevant MeSH terms: Alcoholism; Dutasteride

Study Results

Participant Flow

Pre-assignment Detail	4 subjects excluded during screening due to medical or laboratory exclusion (n=3) or current drug dependence (n=1); 4 subjects lost interest in participation following screening and prior to randomization to treatment arm resulting in 37 subjects available for randomization to treatment arm

Arm/Group Title	Dutasteride	Placebo
Arm/Group Description	dutasteride (1 mg oral daily dose) for 8-week treatment period Dutasteride: dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period	placebo daily for 8-week treatment period placebo: placebo capsules in same number as active drug, daily for 8-week treatment period
Period Title: Overall Study
STARTED	20	19
COMPLETED	18	18
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Dutasteride	Placebo	Total
Arm/Group Description	dutasteride (1 mg oral daily dose) for 8-week treatment period Dutasteride: dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period	placebo daily for 8-week treatment period placebo: placebo capsules in same number as active drug, daily for 8-week treatment period	Total of all reporting groups
Overall Participants	20	19	39
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 95%	17 89.5%	36 92.3%
>=65 years	1 5%	2 10.5%	3 7.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.95 (10.21)	54.95 (7.44)	52.90 (9.08)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	20 100%	19 100%	39 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%	1 5.3%	2 5.1%
Not Hispanic or Latino	19 95%	18 94.7%	37 94.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 5%	1 5.3%	2 5.1%
White	18 90%	18 94.7%	36 92.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5%	0 0%	1 2.6%
Region of Enrollment (participants) [Number]
United States	20 100%	19 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Change Number of Standard Drinks Per Week.
Description	Change in Average Standard Drinks (14 gr ethanol) per week: last 2 weeks of treatment (wk 7-8) minus baseline average drinking average from baseline 90 day drinking history
Time Frame	Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dutasteride	Placebo
Arm/Group Description	dutasteride (1 mg oral daily dose) for 8-week treatment period Dutasteride: dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period	placebo daily for 8-week treatment period placebo: placebo capsules in same number as active drug, daily for 8-week treatment period
Measure Participants	18	18
Mean (Standard Error) [standard drinks per week]	-26.2 (4.6)	-25.5 (4.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Standard Drinks Per Week - Moderation by Genetic Variation
Description	Moderation of primary outcome measure [change in standard drinks per week from baseline to end point (average weeks 7 and 8 of treatment)] by genetic variation rs12529 in neuroactive steroid biosynthetic enzyme gene AKR1C (AKR1C3*2 C-allele associated with alcohol use disorder)
Time Frame	Baseline (average weekly drinking for 90 day period prior to screening) vs. End Point (average weekly drinking weeks 7 and 8 of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AKR1C3*2 C/C Genotype + Dutasteride	AKR1C3*2 C/C Genotype + Placebo	AKR1C3*2 G-carriers + Dutasteride	AKR1C3*2 G-carriers + Placebo
Arm/Group Description	AKR1C3*2 C/C genotype subjects in dutasteride arm (1 mg daily for 8 wks)	AKR1C3*2 C/C genotype subjects in placebo arm placebo: placebo capsules in same number as active drug, daily for 8-week treatment period	AKR1C3*2 G-carriers in dutasteride arm (1 mg/day x 8 wks)	AKR1C3*2 G-carriers in placebo arm
Measure Participants	8	5	10	13
Mean (Standard Error) [standard drinks per week]	-32.4 (5.4)	-31.2 (13.9)	21.8 (6.9)	-22.3 (3.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dutasteride, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	AKR1C3*2 G-carriers + Dutasteride, AKR1C3*2 G-carriers + Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Dutasteride		Placebo
Arm/Group Description	dutasteride (1 mg oral daily dose) for 8-week treatment period Dutasteride: dutasteride 4 mg loading dose followed by 1 mg daily for 8-week treatment period		placebo daily for 8-week treatment period placebo: placebo capsules in same number as active drug, daily for 8-week treatment period
All Cause Mortality
	Dutasteride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dutasteride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Dutasteride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/20 (55%)		9/19 (47.4%)
Gastrointestinal disorders
Stomach discomfort	4/20 (20%)	4	1/19 (5.3%)	1
Nausea	1/20 (5%)	1	0/19 (0%)	0
General disorders
Tiredness	2/20 (10%)	2	2/19 (10.5%)	4
change in sleep	3/20 (15%)	14	3/19 (15.8%)	6
lightheadness/dizziness	1/20 (5%)	4	1/19 (5.3%)	3
Musculoskeletal and connective tissue disorders
Muscle or joint ache	1/20 (5%)	1	1/19 (5.3%)	6
Nervous system disorders
Headache	2/20 (10%)	2	0/19 (0%)	0
Reproductive system and breast disorders
Reduced libido	2/20 (10%)	6	3/19 (15.8%)	9
Impotence	0/20 (0%)	0	1/19 (5.3%)	5
gynecomastia	1/20 (5%)	2	0/19 (0%)	0

Limitations/Caveats

28% of participants were abstinent for the entire 8-week medication treatment period which reduced ability to detect the hypothesized treatment effects of dutasteride related to alcohol's acute effects on neuroactive steroid production.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.